Project Summary/Abstract High throughput screening promises to help both drug discovery and therapeutic response to personalized medicine. A challenge to the development of tissue constructs is the lack of an effective noninvasive assay that is capable to monitor cellular anatomy and physiology. The major limitation of efficacy testing in in vitro models is the cost and inefficiency of histologic preparation. Our group has recently developed a confocal imaging approach to create images that mimic the contrast mechanisms and even the appearance of standard Hematoxylin and eosin-stained histology nondestructively on whole tissue specimens. Our technique, which is noninvasive and relatively easy to perform, may enable high-throughput cellular analysis of 3D bioprinted skin constructs (3DBPS) such that longitudinal drug screening experiments can be supported. Although 3DBPS can test a variety of disease models and drug targets, we will begin working with squamous cell carcinoma (SCC) as a model, based on our experience in this area. This project builds and characterizes a 3DBPS model of SCC, defines imaging biomarkers for SCC as verified by histology in order to characterize treatment by known chemotherapeutic agents, and monitors drug response using the imaging biomarkers defined for SCC 3DBPS. Data generated will be used as a standard to rapidly and non-destructively screen novel, potential cancer anti-cancer drugs. Successful completion of this project will yield a new drug discovery platform for rapid, parallel and massive testing of chemotherapeutic agents.